ABSTRACT
Background and Aim
In an aging population, stroke is a leading cause of morbidity and mortality. More than 80% of stroke cases in the elderly are ischemic strokes. Stroke is the sixth most common cause of disability globally and the second most common cause after ischemic heart disease (IHD). This study aimed to assess the effects of aspirin alone (monotherapy) and clopidogrel and aspirin (combination treatment) on individuals with acute ischemic stroke.
Methods
This is a Prospective, non‐randomized, and observational study conducted in a tertiary care teaching hospital with 116 acute ischemic stroke patients from January 2023 to September 2024. Clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or aspirin (75 mg per day for 90 days) group.
Results
In our study, the majority of patients were more than 60 years, and the least were less than 40 years in both the groups. Predominant were male than female in both the groups. The mRS 3–6 occurred in three patients in the DAPT group and three patients in the monotherapy group, showing no statistically significant difference. Poor quality of life at 90 days occurred in one patient in the clopidogrel aspirin group and in two in the aspirin group (p = 0.081).
Conclusion
In this observational study, the patients with acute Ischemic Stroke, given treatment with clopidogrel and aspirin, provided significantly better functional outcomes and disability scores in the next 90 days than aspirin alone. However, these findings should be interpreted within the context of an observational design and limited follow‐up.
Keywords: acute ischemic stroke, aspirin, clopidogrel, dual anti‐platelet therapy, observational study
1. Introduction
Stroke continues to be a significant global health issue, with around 7 million new cases each year, ranking as the second greatest cause of mortality and a major contributor to long‐term adult impairment [1]. The World Health Organization defines stroke as a rapidly developing clinical sign of focal, and sometimes global, disturbances in cerebral function that persist for more than 24 h or lead to death, with no identifiable cause other than a vascular origin. Ischemic strokes account for around 80% of all stroke types, with over 15% being preceded by a transient ischemic attack (TIA), a crucial warning event that markedly increases the risk of a later stroke, especially within the initial 48 h [2].
The worldwide incidence of stroke is expanding in older demographic, with projections indicating an increase from 1.1 million cases in 2000 to 1.5 million yearly by 2025 [3]. This trend is same in India, where the incidence of stroke has increased, totaling 1.5 to 2 million new cases annually [4]. In association with TIAs, the ischemic stroke comprises approximately 30% of all strokes. India estimates around 500,000 TIA cases annually, frequently worsened by delayed diagnosis and restricted access to specialized care [5].
Dual antiplatelet therapy (DAPT), the combination of clopidogrel and aspirin, has acquired significance in managing the non‐embolic ischemic stroke [6]. Clopidogrel, an established platelet aggregation inhibitor, works by antagonizing platelet receptors and is widely used across cardiovascular and cerebrovascular domains. Aspirin (acetylsalicylic acid) has antiplatelet actions by irreversibly inhibiting platelet cyclooxygenase, therefore obstructing the formation of thromboxane A₂, a powerful platelet activator. The combination of these two agents enhances platelet inhibition and reduces stroke reoccurrence [7].
Current stroke care guidelines recommend a 21‐day regimen of DAPT for patients with mild ischemic stroke or high‐risk TIA, subsequently transitioning to monotherapy with a single antiplatelet agent [8]. Global trials such as CHANCE and POINT have demonstrated the benefit of DAPT in the early phase following mild stroke or high‐risk TIA, particularly within the first 21 days [9]. However, these findings are majorly on the western population, and the specific factors such as medication adherence, the genetic variability, and associated comorbidities are not reported, which can change the clinical outcomes completely. The phenomenon of resistance to clopidogrel also adds to the complexity in different populations [10]. This emphasizes the need to local data before giving the DAPT to the patients with acute ischemic stroke. The objective of this study is to assess and compare the effect of DAPT and mono therapy on functional outcomes and quality of life (QoL) in Indian patients with acute non‐cardioembolic ischemic stroke. The functional recovery was evaluated using the modified Rankin Scale (mRS), and QoL was assessed with the EQ‐5D instrument over a 90‐day follow‐up period [11, 12]. The study addresses a critical evidence gap by providing population‐specific data on the comparative effectiveness and safety of these two widely used therapeutic regimens in a resource‐limited clinical setting.
2. Methods
2.1. Study Design
This is a prospective, non‐randomized, and observational cohort study conducted in a tertiary care teaching hospital in India from January 2023 to September 2024. The study was designed to reflect real‐world clinical practice, where treatment decisions were made by the treating neurologist rather than through random allocation. This study included all consecutive patients diagnosed with mild, non‐disruptive acute ischemic stroke (AIS) or TIA who received DAPT or aspirin monotherapy.
2.2. Ethical and Consent
The study was approved from the ethical committee at Multi Speciality Hospital in India, and ethical clearance was taken prior to the recruitment.
2.3. Participants
All consecutive adult patients were enrolled based on clinical and radiological confirmation of AIS within 24 h of the symptoms onset with ABCD score ≥ 4. Mild stroke was classified using the NIHSS score (≤ 3). Time for the onset of the symptoms and hospital presentation was recorded for all the patients. Eligibility for thrombolysis followed standard guidelines of 4.5 h. Antiplatelet therapy was initiated within 24 h symptom onset after exclusion of neuroimaging.
The Exclusion criteria included a MRS ≥ 2 at baseline, history of intracerebral hemorrhage or a definitive rationale for anticoagulation, such as the presence of mechanical heart valves. The patient with sensory or visual symptoms, GI bleeding or surgery, life expectancy < 3 months, pregnancy, malignancy recent or past were excluded. A total of 183 patients were assessed for eligibility; 67 were excluded due to predefined criteria and incomplete data. The exclusion was made as 7 patients had the history of intracerebral hemorrhage, 7 were using anticoagulants, 13 didn't had neuroimaging confirmation, and 38 for incomplete baseline data recorded during admission. During the follow‐up period, one patient in the monotherapy group and two in the DAPT group were lost to follow‐up. The remaining 116 participants were included in the study, with 58 patients receiving aspirin monotherapy and 58 receiving DAPT. All participants included had complete baseline and outcome data for the 90‐day follow‐up and were included in the final analysis.
2.4. Interventions
The treatment allocation was non‐randomized; it was administered based on the clinical judgment and the profile of the patient. The patients received either DAPT, that is, Clopidogrel (300 mg loading dose, then 75 mg/day for 90 days) + Aspirin (75 mg/day for 21 days) or Monotherapy group, that is, Aspirin 75 mg/day for 90 days. The assignment was completely on clinical judgment of the treating neurologist, considering the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), risk of recurrence, risk of bleeding, and comorbid conditions. The patients with large artery atherosclerosis, according to TOAST, were more likely to receive DAPT, while those with higher bleeding risk received aspirin monotherapy.
Due to the non‐randomized allocation and the observational design of the study, the imbalance between the treatments was anticipated. To address the issue of confounding variables, the baseline characteristics were systematically recorded and compared between the groups.
2.5. Outcomes
The MRS was the primary outcome measure for functional recovery recorded at baseline and after 90 days. An mRS score of 0–2 was considered a favorable outcome, while > 3 indicates moderate disability or > 5 is taken as severe disability or death. The secondary outcome included health‐related quality of life (QoL) was assessed by ED‐5Q, covering five domains of mobility, self‐care, activities, discomfort, and anxiety/depression. The written consent was waived due to the observational nature of the study, and ethical clearance was taken with ethical number IRB/SIMS/03/25314/2022.
2.6. Statistical Analysis
The descriptive statistics are presented as mean and SD for continuous variables and frequencies for categorical variables. To test the normality, the Shapiro–Wilk test was used. Variables with normal distribution were compared using an independent t‐test, and with non‐normal distribution, the Mann–Whitney test was used at the baseline. Comparing the categorial variables at the baseline Chi‐Square test and Fisher's Exact Test were used. All regression analyses were two‐sided with a prespecified significance level of p < 0.05 and were conducted using SPSS version 20. Functional outcomes based on the mRS and quality‐of‐life outcomes measured using EQ‐5D were compared between treatment groups using chi‐square or Fisher's exact tests as appropriate. A two‐sided p‐value < 0.05 was considered statistically significant for all analyses.
3. Results
A comparison of continuous variables between the DAPT (Aspirin + Clopidogrel) and monotherapy groups, each with 58 patients, revealed many statistically significant changes that may influence treatment results in patients with acute ischemic stroke. The mean age of participants was 64.9 ± 13.5 years in the monotherapy group and 66.9 ± 12.6 years in the DAPT group, with no statistically significant difference between groups (p = 0.42). No significant difference was observed in BMI (p = 0.83) or WBC count (p = 0.82). Serum creatinine, blood glucose and LDL cholesterol were significantly differed. Platelet counts were slightly higher (p = 0.01), and systolic BP was marginally lower (p < 0.001) in the combination group (Table 1).
TABLE 1.
The comparison baseline demographics of both the groups.
| Variable (Mean ± SD) | Monotherapy (n = 58) | DAPT (n = 58) | T/U value | p‐value |
|---|---|---|---|---|
| Age (years) | 64.9 ± 13.5 | 66.9 ± 12.6 | T = −3.21 | 0.42 |
| BMI (kg/m2) | 23.8 ± 3.3 | 23.8 ± 3.4 | T = 0.01 | 0.83 |
| WBC (×109/L) | 8.19 ± 3.69 | 8.20 ± 3.04 | U = 1672 | 0.82 |
| Creatinine (mg/dL) | 0.94 ± 0.85 | 1.02 ± 0.93 | U = 1184 | < 0.001 |
| Blood Glucose (mg/dL) | 141.8 ± 59.8 | 146.9 ± 63.8 | U = 1210 | < 0.001 |
| LDL cholesterol (mg/dL) | 115.2 ± 36.2 | 109.5 ± 37.1 | T = 3.08 | < 0.001 |
| Platelet count (mg/dL) | 234.2 ± 76.2 | 237.6 ± 74.2 | T = −2.56 | 0.01 |
| SBP (mm/Hg) | 152.1 ± 28.6 | 149.5 ± 27.0 | T = 3.34 | < 0.001 |
Note: Continuous variables are presented as mean ± standard deviation. Normality was assessed using the Shapiro–Wilk test. Variables with normal distribution were compared using the independent samples Student's t‐test (reported as t values), while non‐normally distributed variables were compared using the Mann–Whitney U test (reported as U values). The level of significance was taken as < 0.05.
The baseline clinical characteristics comparison has shown no significant differences between both the groups for past stroke, hypertension, TIA, smoking history, and associated comorbidities such as dyslipidemia and coronary heart disease. Stroke severity was also the same at the baseline, with mild stroke was reported in 69% and 71.0% in the monotherapy and DAPT groups. The TOAST classification has shown the differences between both the groups (p = 0.002). The DAPT group had more large artery atherosclerosis cases (29 in DAPT vs. 23 in monotherapy groups), while cardioembolic strokes were only seen in Group A (4 cases). Two categories were used to evaluate the arrival time post‐stroke: either within 24 h or between 24 and 72 h (Table 2). There were no significant differences in acute care access, as 29 patients in Group A (50%) and 33 in Group B (57.9%) arrived within 24 h, while 27 patients in Group A (46.6%) and 24 patients in Group B (42.1%) arrived later (p = 0.198) (Table 2).
TABLE 2.
Comparison of baseline clinical characteristics and stroke subtypes between the groups.
| Variable | Monotherapy (n = 58) | DAPT (n = 58) | χ²/Test statistic | p‐value |
|---|---|---|---|---|
| Stroke | 15 (25.9%) | 13 (22.4%) | χ² = 0.48 | 0.489 |
| Hypertension | 32 (55.2%) | 35 (60.3%) | χ² = 0.67 | 0.414 |
| Diabetes mellitus | 12 (20.7%) | 14 (24.1%) | χ² = 0.54 | 0.464 |
| Dyslipidemia | 4 (6.9%) | 3 (5.2%) | Fisher's exact | 0.753 |
| TIA | 1 (1.7%) | 1 (1.7%) | Fisher's exact | 1.000 |
| Coronary disease | 2 (3.4%) | 4 (6.9%) | Fisher's exact | 0.381 |
| Myocardial infarction | 1 (1.7%) | 2 (3.4%) | Fisher's exact | 0.740 |
| Atrial fibrillation | 2 (3.4%) | 1 (1.7%) | Fisher's exact | 0.200 |
| Antiplatelet use | 5 (8.6%) | 6 (10.3%) | χ² = 0.24 | 0.623 |
| Current or previous smoking | 27 (46.6%) | 28 (48.3%) | χ² = 0.01 | 0.928 |
| NIHSS ≤ 3 | 40 (69.0%) | 41 (70.7%) | χ² = 0.11 | 0.739 |
| NIHSS > 3 | 18 (31.0%) | 17 (29.3%) | χ² = 0.11 | 0.739 |
| Arrival time ≤ 24 h | 29 (50.0%) | 33 (56.9%) | χ² = 1.66 | 0.198 |
| Arrival time 24–72 h | 27 (46.6%) | 24 (42.1%) | χ² = 1.66 | 0.198 |
| TOAST: LAA | 23 (39.7%) | 29 (50%) | 0.002 | |
| TOAST: SVO | 22 (37.9%) | 22 (37.9%) | 0.002 | |
| TOAST: CE | 4 (6.9%) | 0 (0%) | 0.002 | |
| TOAST: OE | 1 (1.7%) | 1 (1.7%) | 0.002 | |
| TOAST: UD | 6 (10.3%) | 5 (8.6%) | χ² = 17.1 | 0.002 |
Note: Categorical variables are presented as a number (percentage). Comparisons between groups were performed using the chi‐square (χ²) test. Fisher's exact test was used when cell counts were < 5. The level of significance was taken as < 0.05.
The use of medication differed significantly between both the groups. Prior use of antiplatelet therapy was more in the DAPT group than in the monotherapy group (32.7% and 14.1%, respectively; p < 0.001). The DAPT group has shown the higher use of antihypertensive medications, antidiabetic drugs, and statins with statistical significance (p < 0.001). Similarly, the dual therapy group had higher use of antihypertensive medications (51.7% vs. 41.3%), antidiabetic drugs (25.9% vs. 20.5%), and statins (21.3% vs. 11.6%), all with statistically significant differences (p < 0.001) (Table 3). These differences might be due to the clinical judgment and selection criteria as mentioned in the methodology.
TABLE 3.
Comparison of the use of medications among both groups.
| Variable | Monotherapy (n = 58) | DAPT (n = 58) | χ²/Test statistic | p‐value |
|---|---|---|---|---|
| Antiplatelet use | 8 (14.1%) | 19 (32.7%) | χ² = 10.9 | < 0.001 |
| Anti‐HTN meds | 24 (41.3%) | 30 (51.7%) | χ² = 1.15 | < 0.001 |
| Anti‐diabetic meds | 12 (20.5%) | 15 (25.9%) | χ² = 0.47 | < 0.001 |
| Statins | 7 (11.6%) | 12 (21.3%) | χ² = 1.92 | < 0.001 |
Note: Categorical variables are presented as a number (percentage). Comparisons between groups were performed using the chi‐square (χ²) test. The level of significance was taken as < 0.05.
In the monotherapy, 71.3% had an mRS of 0 (no disability), 26.1% had minor disability (mRS 1), and 2.6% had slight disability (mRS 2). In the DAPT group, 73.9% had an mRS of 0, 20.0% had an mRS 1, and 6.1% had an mRS 2. There was no significant difference between both the groups in pre‐stroke functional status.
Table 4 showing mRS scores and EQ‐5D scores after 90 days of treatment. The mRS scores have improved more in the DAPT group as compared to monotherapy group. mRS 0–1 (no disability) was seen in 79.3% monotherapy groups and 82.5% in DAPT group. The lower disability (mRS 2–6) in the latter group (17.5% vs. 20.7%). When considering mRS 0–2, 91.2% of dual therapy patients met the favorable outcome criteria versus 87.9% in the monotherapy group, while moderate‐to‐severe disability (mRS 3–6) was lower with dual therapy (8.8% vs. 12.1%) (Table 4). There was no significant difference in pre‐stroke functional status between the monotherapy and DAPT groups (χ² = 0.854, p = 0.652)
TABLE 4.
Showing the distribution of functional outcome pre‐stroke modified Rankin Scale (mRS) scores.
| mRS score (pre‐stroke) | Monotherapy (n = 58) | DAPT (n = 58) | χ² statistic | p‐value |
|---|---|---|---|---|
| 0 | 41 | 43 | χ² = 0.854 | 0.065 |
| 1 | 15 | 12 | ||
| 2 | 2 | 3 | ||
| Total | 58 | 58 |
QoL as assessed by the EQ‐5D instrument showed that four patients (6.9%) in the Aspirin group and two patients (3.5%) in the dual therapy group reported poor outcomes. Although this result trends in favor of the Clopidogrel + Aspirin group, the difference was not statistically significant (p = 0.081) (Table 5).
TABLE 5.
The mRS scores and ED‐5Q among both the groups after 90 days of treatment.
| Outcome | Time point | Monotherapy | DAPT | Between‐group test (χ²/Fisher) | p‐value |
|---|---|---|---|---|---|
| Modified Rankin Scale (mRS) | |||||
| mRS 0 | Pre‐stroke | 41 (70.7%) | 43 (75.4%) | χ² = 0.42 | 0.81 |
| mRS 1 | Pre‐stroke | 15 (25.9%) | 11 (19.3%) | ||
| mRS 2 | Pre‐stroke | 2 (3.4%) | 3 (5.3%) | ||
| mRS 0–1 | 90 days | 46 (79.3%) | 47 (82.5%) | χ² = 0.19 | 0.041 |
| mRS 2–6 | 90 days | 12 (20.7%) | 10 (17.5%) | ||
| mRS 0–2 | 90 days | 51 (87.9%) | 52 (91.2%) | χ² = 0.16 | 0.039 |
| mRS 3–6 | 90 days | 7 (12.1%) | 5 (8.8%) | ||
| EQ‐5D quality of life | |||||
| Poor QoL | 90 days | 4 (6.9%) | 2 (3.5%) | Fisher's exact | 0.081 |
| Acceptable QoL | 90 days | 54 (93.1%) | 55 (96.5%) | ||
Table 6 shows a comparison of poor outcomes between both the groups, stratified by stroke scales. DAPT is associated with fewer poor outcomes across all the categories of mRS: 2–6 (7.9% vs. AOR 1.87), mRS 3–6 (7.0%, AOR 1.96), and poor EQ‐5D scores (3.5%, AOR 1.85). Similarly, monotherapy is associated with the poor quality of life compared to DAPT (Table 5). Specifically, mRS 2–6 occurred in 12.2% (AOR 1.72), mRS 3–6 in 11.3% (AOR 1.85), and poor EQ‐5D outcomes in 9.6% (AOR 1.92). These results highlight a consistent advantage of dual therapy in reducing disability and improving quality of life (Table 6).
TABLE 6.
The comparison of poor outcomes of mRS scale and ED‐5Q scale among both the groups.
| Outcome | Monotherapy (n = 58) | DAPT (n = 57) | Number of poor outcomes (%) | Adjusted odds ratio (95% CI) |
|---|---|---|---|---|
| mRS score: 2 to 6 (No stroke) | 14 | 5 | 9 (7.9%) | 1.87 (1.05–3.33) |
| mRS score: 3 to 6 (No stroke) | 11 | 3 | 8 (7.0%) | 1.96 (1.04–3.71) |
| Poor QoL (No stroke) | 7 | 3 | 4 (3.5%) | 1.85 (1.02–3.46) |
| mRS score: 2 to 6 (Stroke) | 29 | 15 | 14 (12.2%) | 1.72 (1.10–2.69) |
| mRS score: 3 to 6 (Stroke) | 23 | 10 | 13 (11.3%) | 1.85 (1.14–3.01) |
| Poor QoL (Stroke) | 20 | 9 | 11 (9.6%) | 1.92 (1.08–3.41) |
4. Discussion
In acute ischemic stroke patients, this comparison of Aspirin monotherapy and DAPT (Clopidogrel + Aspirin) showed that combination therapy offers a slight but statistically significant advantage in terms of improving quality of life at 90 days, lowering disability, and improving clinical outcome [13].
The functional recovery was better in the DAPT group similar to the previous studies that have shown the use of this therapy and lower incidence of unfavorable outcomes [14]. The findings suggest a trend toward better functional outcomes with DAPT, although causal inference is limited due to the observational study design. The functional advantage of dual therapy was further supported by similar patterns in EQ‐5D quality of life measurements and more severe disability (mRS 3–6) [15]. The findings are consistent with previous findings that show that use of DAPT reduces the risk of recurrent stroke in early stages after a mild stroke [16]. Previous studies have suggested that short‐term DAPT may improve early stroke outcomes; however, bleeding complications and recurrence risk were not assessed in the present analysis.
Baseline characteristics were generally comparable across several major clinical variables; however, some differences in laboratory parameters and medication use were observed between groups, which may reflect real‐world treatment allocation in clinical practice. The DAPT was not shown to be affected by the variations, such as higher mean age, low LDL, and high mean age. Although several major vascular risk factors were similarly distributed between groups, some baseline differences were present, which should be considered when interpreting the findings.
The studies have shown the significant differences in the distribution of stroke risk factors, including coronary artery disease, diabetes, hypertension, and dyslipidemia, among the groups [17]. According to the TOAST and CHANCE trials, short‐term DAPT may reduce the risk of recurrent stroke in selected populations. However, recurrence outcomes were not directly evaluated in the present study [18].
There was a non‐statistical difference in bad EQ‐5D outcomes, suggestive of a limited role of DAPT on quality of life in recorded duration and might require longer durations for acting on the same. When compared to Aspirin monotherapy, DAPT produces noticeably superior clinical results in patients with acute ischemic stroke, as shown by disability (mRS) and health‐related quality of life (EQ‐5D), according to the current comparative study. In the early stages of stroke recovery, when the best antithrombotic treatments can affect long‐term neurological outcomes, these findings are particularly pertinent [19].
From a pathophysiological perspective, the two medication's complementing modes of action may be the reason for dual therapy's greater effectiveness [20, 21]. Aspirin works by permanently blocking the formation of thromboxane A2 by inhibiting cyclooxygenase‐1 (COX‐1), whereas Clopidogrel targets the P2Y12 adenosine diphosphate (ADP) receptor pathway, which occurs majorly in the first 14 days [22]. This pharmacodynamic explanation explains the study's observed differences in outcomes, especially the lower percentage of patients in the DAPT group who had mRS 2–6 and 3–6 scores.
DAPT was found to have advantages beyond preventing stroke recurrence, better neurological conditions according to FASTER trials, including improved functional recovery and a decrease in complaints of low quality of life [23, 24]. Furthermore, when it started within 24 h of the onset of symptoms, short‐term DAPT decreased the chance of stroke recurrence without raising the risk of significant bleeding, according to a meta‐analysis [24].
Notably, the findings are reinforced by the baseline similarity of both groups with respect to age, comorbidities, inflammatory markers, and stroke severity. The little variations in LDL cholesterol and creatinine were clinically insignificant but statistically significant, most likely due to individual variability rather than systemic bias [25]. Better quality of life indicates a trend towards more favorable recovery trajectories, even though it is not statistically significant in EQ‐5D measurements. This is in line with the objectives of patient‐centered care, which emphasize not only survival but also restoration to normal functioning and less caregiving stress [12]. DAPT is advised for 21 to 90 days following a small stroke or high‐risk TIA, according to current guidelines (AHA/ASA 2021), which emphasizes that patient selection and duration are crucial for optimizing benefit and minimizing harm.
Overall, this study supports the use of Clopidogrel + Aspirin in carefully selected patients during the early phase of ischemic stroke. The noted gains in mRS and EQ‐5D results support previous research and demonstrate the value of dual therapy in improving post‐stroke functional status and quality of life in addition to lowering the risk of stroke recurrence.
4.1. Limitation
The non‐randomized, single‐center design introduces potential selection bias and confounding by indication. Multivariable regression analyses were performed to adjust for key confounders, including age, sex, stroke severity, vascular risk factors, prior antiplatelet use, and concomitant medications. Although multivariable adjustment was performed, residual confounding cannot be excluded due to the observational and non‐randomized nature of the study. Also, the casual interface may limit the generalizability as treatment allocation reflects real‐world practice. Due to the nature of the effect of both therapies on study stroke recurrence has not been studied.
The large, randomized studies with longer follow up are required to confirm the long term benefits of these drugs This study has limited acceptability as this was a non‐randomized, single‐center study with potential selection bias, also the groups were different on certain parameters on the baseline.
5. Conclusion
This prospective observational study found that DAPT with Clopidogrel and Aspirin showed modestly better functional outcomes and lower disability rates in 90 days as compared with aspirin monotherapy in acute ischemic stroke patients. As the study did not assess the bleeding complications. The benefits were consistent across stroke and non‐stroke subgroups, with fewer adverse outcomes observed in the dual therapy group.
As this study did not directly assess bleeding complications or stroke recurrence, no definitive conclusions regarding safety or recurrence prevention can be drawn. Given the non‐randomized design, the observed associations should not be interpreted as causal. Larger, randomized controlled studies with dedicated safety and recurrence endpoints are required to confirm these findings.
Author Contributions
Sohailuddin Mohammad, Hemaakshi Gupta, and Dipinder Deep Bhat worked on the conceptualization of the study. Hemaakshi Gupta led the methodology, investigation, data collection, validation, and formal analysis. Tirunagari Navya Sree and Anveshak contributed to original draft preparation and data management. Summaiah Asim, Mohammed Faizan Ahmed, and Pooja Pancholi assisted in literature review and manuscript editing. Younes Nabgouri, Mohammed Abdul Mateen, and Nagham Al Dirani were responsible for supervision, project administration, and final manuscript approval. All authors contributed to manuscript preparation and approved the published version.
Funding
The authors have nothing to report.
Ethics Statement
The study was approved by the ethical committee at Multi Speciality Hospital in Hyderabad, India, and ethical clearance was taken with ethical number IRB/SIMS/03/25314/2022.
Conflicts of Interest
The authors declare no conflicts of interest.
Transparency Statement
The lead author, Nagham Al Dirani, affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Data Availability Statement
The data is available on request due to privacy restrictions. The data supporting the findings of the study are available from the corresponding author upon reasonable request. As the dataset contains human participant information, the scripts used for the analysis can be shared with approval from the institutional ethical committee.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data is available on request due to privacy restrictions. The data supporting the findings of the study are available from the corresponding author upon reasonable request. As the dataset contains human participant information, the scripts used for the analysis can be shared with approval from the institutional ethical committee.